Tonelli et al.

Biology of Sex Differences 2011, 2:12

http://www.bsd-journal.com/content/2/1/12

RESEARCH Open Access

Women with knee osteoarthritis have more pain

and poorer function than men, but similar
physical activity prior to total knee replacement
Shalome M Tonelli1, Barbara A Rakel1*, Nicholas A Cooper2, Whitney L Angstom1 and Kathleen A Sluka2

Abstract
Background: Osteoarthritis of the knee is a major clinical problem affecting a greater proportion of women than
men. Women generally report higher pain intensity at rest and greater perceived functional deficits than men.
Women also perform worse than men on function measures such as the 6-minute walk and timed up and go tests.
Differences in pain sensitivity, pain during function, psychosocial variables, and physical activity levels are unclear.
Further the ability of various biopsychosocial variables to explain physical activity, function and pain is unknown.
Methods: This study examined differences in pain, pain sensitivity, function, psychosocial variables, and physical
activity between women and men with knee osteoarthritis (N = 208) immediately prior to total knee arthroplasty.
We assessed: (1) pain using self-report measures and a numerical rating scale at rest and during functional tasks, (2)
pain sensitivity using quantitative sensory measures, (3) function with self-report measures and specific function
tasks (timed walk, maximal active flexion and extension), (4) psychosocial measures (depression, anxiety,
catastrophizing, and social support), and (5) physical activity using accelerometry. The ability of these mixed
variables to explain physical activity, function and pain was assessed using regression analysis.
Results: Our findings showed significant differences on pain intensity, pain sensitivity, and function tasks, but not
on psychosocial measures or physical activity. Women had significantly worse pain and more impaired function
than men. Their levels of depression, anxiety, pain catastrophizing, social support, and physical activity, however,
did not differ significantly. Factors explaining differences in (1) pain during movement (during gait speed test)
were pain at rest, knee extension, state anxiety, and pressure pain threshold; (2) function (gait speed test) were sex,
age, knee extension, knee flexion opioid medications, pain duration, pain catastrophizing, body mass index (BMI),
and heat pain threshold; and (3) physical activity (average metabolic equivalent tasks (METS)/day) were BMI, age,
Short-Form 36 (SF-36) Physical Function, Kellgren-Lawrence osteoarthritis grade, depression, and Knee Injury and
Osteoarthritis Outcome Score (KOOS) pain subscale.
Conclusions: Women continue to be as physically active as men prior to total knee replacement even though
they have significantly more pain, greater pain sensitivity, poorer perceived function, and more impairment on
specific functional tasks.

Background affected joint. Prior to TKR, women have greater pain

Osteoarthritis (OA) of the knee affects a greater percen- than men when measured using self-report surveys such
tage of women than men and can severely impact a per- as the Western Ontario and McMaster Universities
son’s function and quality of life [1,2]. When Arthritis Index (WOMAC) and Knee Society Scale [3-6].
osteoarthritis becomes severe, total knee replacement A greater decrease in perceived function is also reported
(TKR) is indicated to improve pain and function of the for women when compared with men with knee
osteoarthritis as measured by the Knee Society Score
and the WOMAC [3-6]. Similarly, physical function
* Correspondence: barbara-rakel@uiowa.edu
1
College of Nursing, University of Iowa, Iowa City, IA, USA
tests, such as the 6-minute walk test and the timed up
Full list of author information is available at the end of the article and go, show worse scores for women with knee
© 2011 Tonelli et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Tonelli et al. Biology of Sex Differences 2011, 2:12
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osteoarthritis when compared to men [7,8]. This
decrease in function in women is associated with lower
quadriceps strength as measured by isometric maximal
voluntary contraction [8,9].
It is known that healthy women and men differ on
quantitative sensory testing measures including pressure
pain threshold, heat, and cold measures [10-13]. It is
unknown if those differences in pain sensitivity persist
in populations with chronic knee pain. Women and
men may also differ on psychosocial factors. Women
have higher rates of depression whether they have
chronic pain or are pain free [14]. While pain catastro-
phizing is predictive of future chronic pain development,
disability and pain intensity [15-17], gender differences
in pain catastrophizing in people with late stage osteoar-
thritis are not known. One possibility is that increased
pain and reduced function in women can be attributed
to differences in psychosocial variables.
It would be expected that since perceived function and
physical function tests are reduced in women with
osteoarthritis [3,5-8] that daily physical activity mea-
sured by accelerometry would be similarly decreased.
Accelerometry in people with early osteoarthritis show
less time spent doing vigorous activities with men
spending more time doing moderately and vigorously
intense activity than women [18,19]. Accelerometry in
people with late osteoarthritis show also reductions in
physical activity; these reductions also occur at lower
activity levels [20]. However, it is not clear if these sex
differences in physical activity also occur when osteoar-
thritis becomes more severe prior to surgery for total
knee replacement, and if pain during function or if psy-
chosocial variables contribute to physical activity levels.
The purpose of the current study was to determine if
(1) women and men with late stage OA differ signifi-
cantly on pain at rest and during movement, pain sensi-
tivity using quantitative sensory testing, function,
psychosocial variables, and physical activity levels imme-
diately prior to TKR, and (2) which variables explain the
differences in pain, function and physical activity.
Methods
Subjects were recruited from a large teaching hospital
through the orthopedics joint replacement clinic and
were invited to participate if they were indicated for uni-
lateral TKR for osteoarthritis. Data collection occurred
from June 2008 through to December 2010. Eligible
subjects were approached by a study recruiter and the
informed consent process was completed. Consenting
subjects were screened for sensation and ability to fol-
low directions using three items from the Mini Mental
State Exam (MMSE). A total of 385 subjects were
approached and 208 participated in the study (138
women and 70 men). A total of 96 declined to
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participate and 81 did not meet eligibility criteria due
to: other severe untreated painful conditions (N = 26),
stroke or central nervous system lesion (N = 17), sche-
duling issues (N = 17), sensory impairment (N = 10),
current prisoner (N = 7), cognitive impairment (N = 2),
or wheelchair bound (N = 2). Refusal rates were not sig-
nificantly different (P = 0.10) between women (22.7%)
and men (30.7%). Eligible and consenting subjects com-
pleted the research testing during their preoperative
investigation clinic visit, which typically occurred 1 week
prior to the surgery date.
The outcome measures were collected during the visit
by a trained research assistant who was a registered
nurse or physical therapist. We assessed (1) pain using
self-report measures (Brief Pain Inventory (BPI), Knee
Injury and Osteoarthritis Outcome Score (KOOS),
Short-Form 36 (SF-36)) and with a 0 to 20 numerical
rating scale (NRS) at rest and during function tests, (2)
pain sensitivity using quantitative sensory measures,
including pressure pain thresholds, heat pain thresholds,
and heat tolerance, (3) psychosocial variables including
depression (Geriatric Depression Scale), anxiety (State
Trait Anxiety Inventory), pain catastrophizing (Pain Cat-
astrophizing Scale), and social support (Social Provisions
Scale), (4) function with self-report measures (KOOS,
SF-36), specific function tasks (timed walk, maximal
active flexion and extension), and (5) physical activity
using accelerometer (average metabolic equivalent tasks
(METS)/day and average steps/day).
Outcome measures
Demographics
The following information was collected from subjects
and their medical records: gender, age, race, marital sta-
tus, education, income, duration of knee pain, OA grade
(Kellgren-Lawrence), pain or OA in the contralateral
knee, height and weight, and analgesia intake.
Pain
0 to 20 NRS
Pain intensity at rest and during flexion, extension, and
walking was measured on a 0 to 20 point NRS with 0
anchored with ‘no pain’ and 20 anchored with ‘most
intense pain imaginable’. NRS is strongly correlated with
other pain scales such as visual analog scales (r = 0.91
to 0.95) [21-23] and is associated with higher compli-
ance and lower failure rates in older adults [22].
BPI
The BPI was originally designed to measure pain in can-
cer patients, but has been determined to be a valid tool
for pain measurement in other types of chronic pain
including musculoskeletal pain in older adults [24]. The
BPI intensity scale consists of four items where subjects
rate their pain intensity (0 = no pain, 10 = pain as bad
Tonelli et al. Biology of Sex Differences 2011, 2:12
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as you can imagine) while the BPI interference scale has
seven items asking subjects to rate pain interference in
aspects of daily functioning (0 = does not interfere, 10 =
interferes completely). The BPI has adequate internal
consistency for both the intensity score (0.85) and the
interference score (0.88) [24] as well as acceptable test-
retest reliability (r = 0.58 to 0.95) and validity (Cronbach
a ≥ 0.85) [25].
Hyperalgesia (quantitative sensory testing)
Pressure pain threshold (PPT)
Pressure was applied to sites around the operative knee
with an electronic pressure algometer (Somedic, Some-
dic AB, Box 194, SE-242 22 Hörby, Sweden). Pressure
was applied using a 1 cm2 surface at a rate of 40 kPa/s.
The subject was instructed to push a button when the
pressure sensation first became painful.
Heat pain threshold (HPThr)
Contact heat was applied to sites around the operative
knee with a 16 mm × 16 mm surface thermode (Medoc
TSA; Medoc Ltd 1 Ha’dekel St., Ramat Yishai 30095,
Israel) that increases in temperature at a rate of 1°C/s.
The subject was instructed to click a button when the
heat sensation first becomes painful (heat pain
threshold).
Heat pain tolerance (HPTol)
After the heat threshold test, the temperature returned
to baseline. The thermode device again provided
increasing heat and subjects were instructed to click the
button when the heat reached the most heat tolerable.
The device safety mechanism is programmed to stop
prior to skin damage.
Inter-rater reliability was determined at the beginning
of the study and as needed throughout the study for
pain sensitivity measures. Intraclass correlations ranged
from 0.87 to 0.97 for pressure pain threshold, 0.70 to
0.92 for heat pain threshold, 0.72 to 0.98 for heat pain
tolerance.
Perceived pain and function
KOOS
The KOOS was developed from the WOMAC as a
knee-specific self-report assessment instrument and has
been validated in subjects with knee OA [26]. The
KOOS consists of five subscales: (1) Pain, (2) Other
symptoms, (3) activity in daily living (ADL), (4) function
in sport and recreation (Sport/Rec), and (5) knee related
quality of life (QoL). The last week is taken into consid-
eration when answering the questions. Standardized
answer options are given (five Likert boxes) and each
question receives a score from 0 to 4. The scores are
transformed to a 0 to 100 score (0 = extreme symptoms
to 100 = no symptoms) for each subscale.
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SF-36 Health Survey
The SF-36 contains 36 questions to measure self-
reported functional health and well-being. It is a practi-
cal, reliable (a > 0.85), and valid measure of physical
and mental health [27]. The SF-36 provides scores for
each of eight health domains: (1) Physical Function, (2)
Role - Physical (limitations due to physical health sta-
tus), (3) Bodily Pain, (4) General Health, (5) Vitality, (6)
Social Functioning, (7) Role - Emotional (limitations due
to mental health status), and (8) Mental Health. Items
are transformed to a 0 to 100 (0 = worse health to 100
= perfect health) score.
Function tests
Range-of-motion measurements
Maximum active flexion and extension were measured
using a long-arm goniometer. The subject was placed in a
supine position on an examination table. The goniometer
was aligned with the stationary arm along the lateral mid-
line of the femur toward the greater trochanter, the axis at
the lateral epicondyle of the femur, and the moving arm
along the lateral midline of the fibula aligned with the fib-
ular head and lateral malleolus. For active extension a
towel roll was placed under the ankle to allow for the
greatest extension. Goniometer measures have concordant
validity with radiography of 0.97 to 0.99 [28-31]. Intraclass
correlation coefficients (ICCs) were 0.52 to 0.69 for active
extension and 0.91 to 0.97 for active flexion. The lower
ICC scores for active extension are related to the fact that
extension scores range from 0 to 3 degrees in healthy indi-
viduals and are consistent with studies testing reliability of
extension and flexion using a long arm goniometer [32].
Gait speed test
Subjects were asked to walk ‘as fast as you safely can’ for
15 s down a straight hallway with the research assistant
timing them with a stopwatch and measuring the dis-
tance traveled in inches. ICC scores ranged from 0.88 to
0.99 for gait speed distance. Gait speed has an inter-
rater agreement of 89% to 94% [33] and moderate test-
retest reliability (ICC = 0.56) [34].
Psychosocial variables
Geriatric Depression Scale - Short Form (GDS-SF)
The GDS-SF is a depression screening tool that has five
self-report items with a response format of ‘yes’ or ‘no’.
The five-item GDS-SF has been validated in many dif-
ferent older populations and has as sensitivity of 0.94,
specificity of 0.81, and good test-retest reliability (! =
0.84) [35,36]. Scores of ≥ 3 were classified as positive for
depressive symptoms.
State Trait Anxiety Inventory (STAI)
The STAI is a self-report tool that includes separate
measures for state and trait anxiety [37]. State anxiety
Tonelli et al. Biology of Sex Differences 2011, 2:12
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reflects a transitory emotional state with the scale con-
sisting of 20 statements that ask the subject to describe
rate feelings at a particular moment on a four-point
scale ranging from ‘not at all’ to ‘very much so’. In con-
trast, trait anxiety reflects relatively stable individual dif-
ferences in anxiety with the scale consisting of 20
statements describing how the subject generally feels
rated on a four-point scale ranging from ‘almost never’
to ‘almost always’. Scores on the STAI have a direct
interpretation: high scores on their respective scales
mean more trait or state anxiety and low scores mean
less. The STAI has been validated in older populations
with adequate internal consistency (a = 0.88 to 0.94)
and test-retest reliability (r = 0.51 to 0.58) [38].
Pain Catastrophizing Scale (PCS)
This scale measures three dimensions of pain catastro-
phizing (rumination, magnification, and helplessness). It
is a 13-item self-report scale that assesses the degree to
which subjects have different thoughts and feelings
when experiencing pain and is determined with a five-
point frequency scale ranging from ‘not at all’ to ‘all the
time’. Higher scores indicate more pain catastrophizing.
The PCS was originally developed by Sullivan and col-
leagues [39] and has adequate reliability in adult samples
(a = 0.93 to 0.95; test-retest r = 0.75) with good conver-
gent validity with self-reported anxiety (r = 0.32) [40,41].
Social Provisions Scale (SPS)
This scale measures the construct of social support
[42,43] and has been validated for usage with popula-
tions of older adults with convergent validity (r = 0.18
to 0.22) to morale and friend contact [44]. The SPS has
24 items that are rated as 1 (strongly agree) to 4
(strongly disagree) with half of the items worded as
positive and half as negative. Negative items are reversed
for scoring to allow for higher scores to indicate more
social support.
Physical activity
Accelerometer
An ActivPal accelerometer (PAL Technologies Ltd, 50
Richmond Street, Glasgow G1 1XP, Scotland, UK) was
used to objectively record physical activity. Subjects
wore the accelerometer for 1 week or until their surgery
date, whichever came first. Subjects with less than 2
days of measurement (due to surgery date or device
malfunction) were excluded from this analysis resulting
in a subsample size of 176 subjects. The range of mea-
surement was 2 to 11 days (mean = 5.91 ± 1.77). The
subjects wore the accelerometer taped to the anterior
thigh as directed by the manufacturer and were
instructed to wear the device continuously, removing
the device only for water activities (bathing/swimming)
as the device was not waterproof. The ActivPal uses
proprietary algorithms to calculate the amount of time a
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subject spends sitting, standing, and walking and also
provides an estimate for energy expenditure (METS).
Accelerometers have been used in populations of older
adults with OA [18,45]. Accelerometers have adequate
validity in older adults (r = 0.6) when compared to a cri-
terion measure of energy expenditure [46] and high
reliability between units (ICC = 0.97 to 0.99) for the raw
data of activity counts and steps [47]. While new
research suggests an overall ICC of 0.57 for the ActivPal
METS calculation compared to indirect calorimetry [48]
the METS equation was more accurate at slower walk-
ing speeds and while sedentary which are likely in our
population of older adults with arthritis.
Statistical analysis
Univariate and multivariate analyses were conducted
using SPSS for Windows V. 17.0 (SPSS, Chicago, IL,
USA). Univariate t tests were first used to determine if
there were significant differences between women and
men for the following variables: age, BMI, medication
intake, pain, perceived function, psychosocial variables,
functional tests, and quantitative sensory measures. A c2
test was used for the categorical variables such as race,
marital status, education, income, pain duration, OA
grade, contralateral pain or OA, and depression. Bonfer-
roni adjustments were made for multiple univariate
comparisons on the same measure (SF-36, KOOS, accel-
erometry) to control for error. Multiple linear regression
was conducted using a stepwise selection procedure to
determine the best combination of variables to explain
the variation in pain during walking, distance walked
during the gait speed test, and average METS/day calcu-
lated by accelerometry for the population as a whole
and separately for men and women.
Results
Demographic data for both women and men are shown
in Table 1. Women had higher BMI’s on average than
men with indexes of 35.43 ± 7.59 and 33.19 ± 6.59 for
women and men, respectively (P = 0.04). Women also
had significantly lower OA grades on the Kellgren-Lawr-
ence Scale when compared to men (P = 0.03) No signifi-
cant differences (P > 0.05) between women and men
were observed for age, race, marital status, education,
income, duration of knee pain, contralateral knee pain
or OA, and intake of opiate and non-opiate pain medi-
cations. It should be noted, however that income (P =
0.05), pain at rest (P = 0.08) and non-opiate medication
usage (P = 0.06) were close to statistical significance.
Pain
Pain at rest (0 to 20 NRS) did not vary significantly
between women and men with the average resting pain
measured as 3.77 ± 4.37 and 2.67 ± 3.81, respectively (P
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Table 1 Demographics
Women Men P value
Sample (n = 208) 66.3% (n = 138) 33.7% (n = 70)
Age 61.92 (10.03) 61.66 (9.92) 0.86
Race White 93.48% 92.86% 0.23
Black 4.35% 2.86%
Other 2.17% 1.43%
Marital status Married 55.80% 60% 0.54
Single 35.51% 31.43%
Education High school 30.43% 28.57% 0.80
College 60.14% 61.43%
Income US$0 to US$19,999 28.26% 14.29% 0.05
US$20,000 to US$39,999 17.39% 21.43%
US$40,000 to US$59,999 13.77% 11.43%
US$60,000+ 23.19% 37.14%
Duration of knee pain (months) 0 to 35 months 23.19% 25.71% 0.86
36 to 59 months 19.57% 21.43%
> 60 months 56.52% 52.86%
OA grade 3 32.61% 18.57% 0.03*
4 60.14% 74.29%
Contralateral knee pain 78.26% 72.86% 0.39
Contralateral knee OA 14.49% 15.71% 0.84
BMI 35.43 (7.59) 33.19 (6.59) 0.04*
Pain at rest (0 to 20) 3.77 (4.36) 2.67 (3.81) 0.08
Non-opiate medication (acetaminophen equivalent) 980.84 (1,107.9) 681.79 (1,048.53) 0.06
Opiate medication (morphine equivalent) 6.76 (15.71) 3.86 (12.19) 0.14
BMI = body mass index; OA = osteoarthritis.
* = significance < 0.05

= 0.08). Pain intensity during function tasks (gait speed
test, active flexion and extension) is shown in Figure 1.
Women had significantly higher pain intensity (7.34 ±
5.69) than men (5.69 ± 4.95) (P = 0.04) during the gait
speed test. Women also reported higher pain intensity
during active knee extension: women 8.40 ± 6.43 and
men 5.93 ± 5.44 (P = 0.004) but not during active flex-
ion (P = 0.06). The BPI Intensity scores showed women
had significantly more intense pain averaging 5.4 ± 1.69
compared to men’s average of 4.41 ± 2.02 (P = 0.001).
Women also had significantly worse pain than men on
both the SF-36 Pain subscale and KOOS Pain subscale
(note that a lower score for women indicates more
impairment or worse pain) (P < 0.05) (see Table 2).
Significant predictors of pain with walking utilizing
regression included pain at rest, degrees of active knee
extension, state anxiety, and pressure pain threshold.
These variables explain 24.1% of the variance in pain
with movement (Table 3). Variables not significant in
the model included sex, age, BMI, OA grade, depression,
medication usage, pain duration, pain catastrophizing,
active knee flexion, and the thermal threshold and toler-
ance. These predictor variables were then analyzed for
women and men as separate groups and it was found
that pain at rest, active knee extension, and pressure
pain thresholds were predictive of pain with movement
for women (R2 = 0.268) while pain at rest and pressure
pain thresholds were predictive for men (R2 = 0.181);
thus, active knee extension was an additional predictor
for women. Variables not significant in the full model
included sex, age, BMI, OA grade, depression, medica-
tion usage, pain duration, pain catastrophizing, active
knee flexion, and the thermal threshold and tolerance.
Function
Functional measures are presented in Figure 1 and
Table 2. Women had significantly poorer active knee
extension then men with a loss of 6.83° from full exten-
sion versus 5.07° for men (P = 0.048) but not differ sig-
nificantly from men on active knee flexion (P = 0.43).
The distance traveled during the gait speed test differed
significantly between women and men with women
averaging a distance traveled of 111.7 inches less than
men (P = 0.001). Self-report function measures using
the SF-36 physical function (PF) subscale showed
women have significantly worse perceived function than
men (lower scores) with scores of 31.08 ± 19.48 and
38.87 ± 24.02, respectively (P = 0.018). Similarly, women
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Figure 1 Pain and function scores between men and women. Significant differences occurred for walking pain, extension pain, walking
distance and knee extension (*P < 0.05).

have significantly worse perceived function on the depression, non-opioid medications, anxiety, resting
KOOS ADL subscale with scores of 52.51 ± 19.47 for pain, pressure pain thresholds, and heat pain tolerance.
women and 61.09 ± 22.05 for men (P = 0.007).
Significant predictors of function, measured by dis- Pain sensitivity (quantitative sensory tests)
tance on the gait speed test, utilizing regression included PPT, HPThr, and HPTol data are presented in Table 5.
knee flexion and extension, age, sex, current opioid Women had significantly lower pain thresholds (greater
medication usage, pain duration, pain catastrophizing, sensitivity) to pressure and heat stimuli and lower pain
BMI, and HPThr. These variables explained 34.5% of tolerance to heat stimuli than men. On the affected
the variation in function (Table 4). These predictor vari-
ables when analyzed separately for women and men Table 3 Pain regression (dependent variable was pain
showed age, active knee flexion, opioid medications, with gait speed 0 to 20 NRS)
pain catastrophizing, and BMI were predictive of gait Predictor variable b Standard error P value
speed for women (R2 = 0.312) and active knee extension
All subjects:
and age (R2 = 0.129) were predictive in men. Variables
Pain at rest 0.400 0.096 < 0.001
not significant in the model included OA grade,
Knee extension 0.193 0.057 0.001
State anxiety 0.075 0.042 0.081
PPT -0.005 0.002 0.024
Table 2 Self-reported pain and function for Short-Form
F value Significance Model fit
36 (SF-36) and Knee Injury and Osteoarthritis Outcome
Overall model 12.713 < 0.001 R2 = 0.241
Score (KOOS); higher scores indicate better health/fewer
impairments Women:
Pain at rest 0.421 0.103 < 0.001
Results Women, average (SD) Men, average (SD) P value
Knee extension 0.243 0.062 < 0.001
BPI Severity 5.40 (1.69) 4.41 (2.02) 0.001*
PPT -0.010 0.004 0.018
SF-36 Pain 34.68 (18.23) 45.98 (23.57) < 0.001*
Women only model 15.295 < 0.001 R2 = 0.267
SF-36 PF 31.08 (19.48) 38.87 (24.02) 0.018*
Men:
KOOS Pain 44.08 (18.71) 50.77 (17.58) 0.020*
Pain at rest 0.422 0.151 0.007
KOOS ADL 52.51 (19.47) 61.09 (22.05) 0.007*
PPT -0.005 0.003 0.086
ADL = activity in daily living; BPI = Brief Pain Inventory; PF = physical
function.
Men only model 6.408 0.003 R2 = 0.181
* = significance < 0.05 NRS = numerical rating scale; PPT = pressure pain threshold.
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Table 4 Function regression (dependent variable was gait Table 6 Psychosocial measures
speed test) Psychosocial Women, average Men, average P
Predictor variable b Standard error P value measure (SD) (SD) value
All subjects: Depression 15.3% 15.9% 0.91
Knee extension -5.013 2.555 0.051 Trait anxiety 34.88 (10.15) 32.81 (9.85) 0.18
Age -8.306 1.695 < 0.001 State anxiety 34.71 (8.94) 32.61 (10.02) 0.15
Knee flexion 3.374 1.180 0.005 Catastrophizing 11.81 (9.52) 11.06 (11.41) 0.63
Sex -80.966 34.717 0.021 Social provisions 80.12 (10.95) 80.92 (9.89) 0.63
Opioid medications -2.489 1.083 0.023
Pain duration 38.014 18.334 0.040 6). Depression rates were the same for women and men
Pain catastrophizing -3.294 1.644 0.047 (15.3% and 15.9%, respectively). Trait anxiety showed
BMI -4.283 2.393 0.075 women scored an average of 34.88 ± 10.15 while men
Heat pain threshold 10.090 5.278 0.058 scored an average of 32.81 ± 9.85 (P = 0.18), which was
F value Significance Model fit similar to the scores of state anxiety of 34.71 ± 8.94 for
Overall model 9.062 < 0.001 R2 = 0.345 women and 32.61 ± 10.02 for men (P = 0.15). PCS
Women: scores were also similar for women and men with scores
Age -9.749 1.802 < 0.001 of 11.81 ± 9.52 and 11.06 ± 11.41, respectively (P =
Knee flexion 3.170 1.094 0.004 0.63). Women and men also reported a similar degree
Opioid medications -2.829 1.097 0.011 of social support as measured by the SPS with average
Pain catastrophizing -3.538 1.847 0.058 scores of 80.12 ± 10.95 for women and 80.92 ± 9.89 for
BMI -4.525 2.625 0.087 men (P = 0.63).
Women only model 10.630 < 0.001 R2 = 0.312
Men: Accelerometry
Knee extension -13.302 5.159 0.012 The accelerometer results are presented in Table 7.
Age -4.755 2.830 0.098 There were no significant differences between women
Men only model 4.358 0.017 R2 = 0.129 and men for the average METS/day (32.33 ± 1.24 vs
BMI = body mass index. 32.51 ± 1.25; P = 0.35), average transitions/day (51.08 ±
16.82 vs 50.53 ± 15.80; P = 0.84), average steps/day
knee, pressure pain thresholds were 234.35 ± 112.73 kPa (4,544.36 ± 2,725.11 vs 5,086.10 ± 2,905.46; P = 0.23), or
for women and 373.23 ± 207.03 kPa for men (P < average time spent vertical/day (3.50 ± 1.80 vs 3.32 ±
0.001), heat pain thresholds were 42.86 ± 3.21°C for 1.70 h; P = 0.52).
women and 44.71 ± 2.78°C for men (P < 0.001), and Variables that significantly explained the variation in
heat pain tolerance were 46.70 ± 2.70°C for women and average METS/day included BMI, age, OA grade,
48.51 ± 1.59°C for men (P < 0.001). Utilizing simple depression, SF-36 PF, and KOOS Pain. These variables
regression with only gender in the model resulted in explained 35.6% of the variation in METS/day for all
gender explaining 16% of the variability in PPT (b = subjects, regardless of gender (Table 8). Gender was not
-138.87, P < 0.001), 7.6% of HPThr (b = -1.86, P < significant in explaining the average METS/day. Other
0.001), and 11.5% of HPTol (b = -1.81, P < 0.001). variables that were not significant in the model were:
pain intensity at rest and during function measures, gait
Psychosocial variables speed distance, degrees of active flexion and extension,
Women and men did not significantly differ on any of pain catastrophizing, state and trait anxiety, social sup-
the psychosocial variables measured in this study (Table port, analgesic intake, and pain duration. Results (data

Table 5 Quantitative sensory testing

Sensory test Women, average (SD) Men, average (SD) P value
Algometer (kPa), affected knee 234.35 (112.73) 373.23 (207.03) < 0.001*
Algometer (kPa), contralateral knee 255.74 (117.75) 414.40 (209.31) < 0.001*
HPThr (°C), affected knee 42.86 (3.21) 44.71 (2.78) < 0.001*
HPThr (°C), contralateral knee 42.73 (3.03) 44.70 (2.30) < 0.001*
HPTol (°C), affected knee 46.70 (2.70) 48.51 (1.59) < 0.001*
HPTol (°C), contralateral knee 47.01 (2.04) 48.70 (1.53) < 0.001*
HPThr = heat pain threshold; HPTol = heat pain tolerance.
* = significance < 0.05
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http://www.bsd-journal.com/content/2/1/12

Table 7 Accelerometer descriptive results pain in people with OA using a comprehensive biopsy-
Accelerometer Women, average Men, average P chosocial approach. When both men and women were
measures (SD) (SD) value considered, physical activity levels were predicted by
Average METS/day 32.33 (1.24) 32.51 (1.25) 0.35 BMI, age, OA grade, depression, SF-36 PF, and KOOS
Average transitions/day 51.08 (16.82) 50.53 (15.80) 0.84 Pain; pain during movement was predicted by pain at
Average steps/day 4,544.36 (2,725.11) 5,086.10 0.23 rest, knee extension, state anxiety and pressure pain
(2,905.46) thresholds; Function was knee flexion and extension,
Average time vertical/ 3.50 (1.80) 3.32 (1.70) 0.52 age, sex, opioid medication usage, pain duration, BMI,
day (h)
and heat pain threshold. Different predictive factors
METS = metabolic equivalent tasks.
were found when the analysis was run with the men
and women separately. We therefore, for the first time,
not shown) were similar when using average steps/day were able to model physical activity levels, pain and
as the outcome variable. function with multiple biopsychosocial variables, and to
determine if there were differences between men and
Discussion women in these variables.
The results of this study show for the first time a dis- Prior studies have modeled a number of different out-
tinct gender difference for pain during movement but comes in people with OA to determine relevant factors
not for pain at rest. We also show for the first time that that can predict outcomes [49-54]. Of direct relevance,
psychosocial variables (depression, anxiety, pain cata- in a sample of 168 OA subjects, sex predicted pain
strophizing, and social provisions) are similar between related outcomes (pain, disability and pain behaviors)
men and women with late-stage osteoarthritis. Similar and catastrophizing mediated the relationship between
to prior studies, pain sensitivity, perceived function and sex and OA pain-related outcomes [55]. Further, in a
function tests are reduced in women compared to men study with 106 OA subjects, pain catastrophizing was a
(see [14]). Surprisingly, while women had significantly significant predictor of pain severity, disability, and func-
worse pain and more impaired function than men, their tion measured by gait [53]. We extended these studies
actual physical activity levels (accelerometry) did not and showed for the first time that quantitative sensory
significantly differ and their OA grade was significantly testing (PPTs) predicted pain with movement, both
lower, that is, less severe. This study developed predic- evoked pain measures. We also show that for pain with
tive models to explain physical activity, function, and movement that knee range of motion was an additional
predictor for women but not for men. We also extend
Table 8 Accelerometer regression (dependent variable these findings and show that for function women had
was average metabolic equivalent tasks (METS)/day) more predictors than men, which included opioid medi-
Predictor variable b Standard error P value cations and pain catastrophizing as predictors of func-
All subjects: tion only for women. However, our studies do not
BMI -0.074 0.013 < 0.001 completely agree with prior studies in that pain catastro-
Age -0.039 0.010 < 0.001 phizing did not predict pain during movement or physi-
OA grade -0.512 0.171 0.003 cal activity. Differences in sample size (106 vs 268), OA
Depression -0.618 0.301 0.042 severity (early vs Pre-total knee arthroplasty), and out-
SF-36 PF 0.011 0.005 0.019 comes measures for pain (AIMS and observed pain
KOOS Pain -0.011 0.006 0.073 behaviors vs pain with movement) and function (self-
F value Significance Model fit report vs gait speed or accelerometry) could underlie
Overall model 12.086 < 0.001 R2 = 0.356 the lack of agreement between prior and the current
Women: study.
SF-36 PF 0.016 0.006 0.004
BMI -0.074 0.015 < 0.001 Pain during rest and movement
Age -0.050 0.011 < 0.001 The current study found no significant gender difference
OA grade -0.466 0.187 0.019 in resting pain but significant gender differences for pain
Women only model 13.284 < 0.001 R2 = 0.354 during movement and self-reported pain as measured by
Men: surveys (BPI, SF-36 Pain subscale, and KOOS Pain sub-
BMI -0.079 0.024 0.002 scale). This is consistent with larger studies that show
Age -0.033 0.017 0.061 worse pain in women compared to men using the Knee
Men only model 6.269 0.004 R2 = 0.218 Society Score survey instrument and the AIMS [5,55].
BMI = body mass index; KOOS = Knee Injury and Osteoarthritis Outcome
Perceived pain measured by surveys reflects both pain at
Score; OA = osteoarthritis; PF = physical function; SF-36 = Short-Form 36. rest and pain during function. The results of this study
Tonelli et al. Biology of Sex Differences 2011, 2:12
http://www.bsd-journal.com/content/2/1/12
suggest that pain during function has the largest impact
on the sex differences found when measuring pain using
self-report survey instruments.
The current study also found that women had lower
Kellgren-Lawrence grades when compared to men,
despite higher pain. These results are in agreement with
prior studies that show women have more severe symp-
toms at the same Kellgren-Lawrence grades when com-
pared to men [56]. This difference in pain in relation to
OA grade is not manifested in early knee OA [18]. It
has been hypothesized that women may have more
severe osteoarthritis than men at the presurgical stage
and wait longer to have surgery [8,57,58]. In fact,
women lose articular cartilage from the proximal tibia at
four times the annual rate of men and from the patella
at a threefold greater rate [59]. In contrast, the current
study showed women have less severe Kellgren-Lawr-
ence scores with a similar duration of pain just prior to
surgery. These data suggest that women have higher
pain despite lower radiographic evidence of OA and
wait a similar length of time to have surgery.
Functional differences in OA
In the current study, women had more deficits on self-
reported function on the SF-36 PF subscale and KOOS
ADL subscale when compared to men, which is in
agreement with prior literature [60]. Similar differences
have also been reported on the Knee Society and AIMS
[3,5,6,55,58]. The current study showed reduced ability
to perform the gait speed test and reduced knee active
range of motion. These data are in agreement and
extend prior studies that show reduced function on the
6-minute walk test, the timed up and go test, and stair
climbing test times [7,8]. The functional differences in
knee OA subjects may in part be due to known differ-
ences in quadriceps muscle strength between women
and men [8,9].
The current study showed that physical activity levels
measured by accelerometry were similar between
women and men immediately prior to surgery, despite
differences in perceived function and functional tasks.
This is in contrast to prior studies that show lower phy-
sical activity levels in women with early OA compared
to men [18]. The gender differences in physical activity
levels are present in healthy populations, where men
spend more time in activities of higher intensity than
women [61,62]. Just prior to surgery, these differences
in physical activity levels seem to disappear. However,
men with OA have better performance on timed walk
tests and stairs than women [63], which agrees with the
results of the current study. Physical function tests are
also similar to perceived function in patients with OA.
This would suggest that physical function tests and per-
ceived function are similar constructs, but that physical
Page 9 of 12
activity, measured by accelerometry, is a different con-
struct. These results also suggest that women with late
stage knee OA continue to move as much as men
despite more pain during movement, greater pain sensi-
tivity, and less functional ability.
Gender differences in pain sensitivity
The current study, in concurrence with prior literature,
shows clear gender differences in pain sensitivity with
women having greater sensitivity to heat, cold, and
mechanical pressure [10-12]. Across the lifespan,
women are more sensitive to heat pain with a nocicep-
tive threshold 1.6°C lower in women than in men [13].
These differences between women and men also occur
for pressure pain thresholds; however, the differences
tend to converge with age, with no gender difference in
pressure pain thresholds at 50 to 70 years [13]. We
found the differences in pressure pain thresholds main-
tained in our population suggesting greater mechanical
pain sensitivity of the deep tissue in women when com-
pared to men when a chronic pain condition such as
OA is present. This relationship of greater clinical and
experimental pain in women has recently been shown in
a chronic shoulder pain population [64].
Psychosocial variables
The current study showed similar scores between
women and men for depression, state anxiety, trait anxi-
ety, pain catastrophizing, and perceived social support.
It is often noted that women have a higher prevalence
of depression [65]. However, we noted no significant dif-
ference with around 15% of both women and men
screening positive for depression. This prevalence rate is
similar to prior studies in chronic pain populations
[14,66]. However, one study found that depression ten-
dency in older Chinese patients with OA explained a
portion of the gender differences in pain [67]. The cur-
rent study similarly, shows that depression explains a
portion of physical activity levels in people with late-
stage OA. Thus, depression may be related to not only
pain, but also function in people with OA.
Sex differences in anxiety are controversial with some
studies finding significant differences while others do
not [68-70]. Some report that men with higher anxiety
also have higher pain intensity [68] while other research
suggests that this relationship is actually stronger in
women [70]. People with OA have higher anxiety than
the general population, which is associated with higher
pain intensity, worse symptoms, and greater healthcare
utilization [71]. However, based on the current study,
these higher anxiety rates appear to occur similarly
among women and men.
Pain catastrophizing has also shown a mixed relation-
ship in pain research with some studies showing no
Tonelli et al. Biology of Sex Differences 2011, 2:12
http://www.bsd-journal.com/content/2/1/12
gender differences [15,72,73] while others showing
women have significantly higher pain catastrophizing
[55]. Prior work shows that pain catastrophizing may
increase daily pain recall, but does not explain differ-
ences in experimental pain [72]. The differences
between studies could be due to studying different
populations (younger vs older; experimental vs clinical
pain) or using different measurement tools for catastro-
phizing. In people with OA, higher pain catastrophizing
scores are associated with greater pain and disability
[49,55], pain 6 weeks after total knee replacement [50],
and poor outcome 6 months after total knee replace-
ment [74]. The current study shows similar catastro-
phizing scores between women and men, and pain
catastrophizing did not explain differences in physical
activity levels. Thus, while pain catastrophizing is clearly
a valuable construct that explains pain in people with
OA, there was no sex differences observed in this
population.
Limitations
Our subjects were recruited from a large teaching hospi-
tal, which may include a different patient population
than other clinical settings. There are many ways to
analyze the differences between women and men. For
our regressions explaining pain, function, and accelero-
metry, we did not perform further analyses to see if the
predictor variables were different for women and men.
That will be focused on and analyzed further as we fol-
low this population through the preoperative to the
postoperative period. The usage of accelerometry is ben-
eficial to help in understanding actual levels of physical
activity, but there are limitations in the validity of the
METS equation as a subject performs higher levels of
physical activity. Further research will focus on how the
ActivPAL variables differ between our OA population
and healthy controls.
Conclusions
Our results clearly show that women have greater pain,
greater pain sensitivity, and reduced function when
compared to men. The role of sex needs to be further
examined to determine if these pain differences are
due to hormonal differences, socialization, or other
factors. Further, we show similar scores between
women and men on psychosocial variables including
depression, anxiety, pain catastrophizing, and social
support suggesting that observed gender differences in
pain and function are not related to psychosocial
differences.
Clinical significance
Clinically, these data suggest that treatments should
place a greater emphasis on pain management and
Page 10 of 12
improving function, particularly in women with OA.
Our data show no sex differences in medication usage,
despite higher pain in women. This could suggest that
women are less sensitive to current pain medication
strategies, and/or that alternative pharmacological and
non-pharmacological pain management strategies would
be more effective in women. Sex differences in predic-
tors of pain and function further suggest pain manage-
ment strategies should be individualized based on
patient characteristics that include sex.
Acknowledgements
This research was supported by the NIH, grant NR009844-02.
Author details
1
College of Nursing, University of Iowa, Iowa City, IA, USA. 2Physical Therapy
and Rehabilitation Science Graduate Program, University of Iowa, Iowa City,
IA, USA.
Authors’ contributions
KS designed the study, analyzed the data and helped draft the manuscript.
BR designed the study and reviewed the manuscript. ST performed the
experiment, analyzed the data, performed statistical analysis and helped
draft the manuscript. NC performed the experiment and assisted with data
analysis. WA assisted with data collection, data analysis, and literature review.
All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 22 June 2011 Accepted: 10 November 2011
Published: 10 November 2011
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doi:10.1186/2042-6410-2-12 Submit your next manuscript to BioMed Central

Cite this article as: Tonelli et al.: Women with knee osteoarthritis have
more pain and poorer function than men, but similar physical activity
and take full advantage of:
prior to total knee replacement. Biology of Sex Differences 2011 2:12.
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